Biology subjects

Thomson, D.

Publications and source records attributed to Thomson, D..

6 recordsLinked to original sources

bioRxiv2025

The influence of larval retention on coral recruitment

Marine broadcast spawners typically exhibit bipartite life-histories with distinct pelagic larvae and benthic phases. The transition between phases shapes benthic populations, but the rate of larval arrival to a reef is largely unknown due to challenges in accurately measuring supply. Once larvae arrive to a reef, reduced current flow and velocity, facilitate the transition from the water column to the benthos for inefficient swimming larvae. Yet, for coral reefs characterised by complex hydrodynamics and tides, slack current conditions typically last 1.5-3 hours and it remains unclear if such short retention periods drive significant recruitment. This study mechanistically examined the effects of water retention on the settlement of coral larvae from the water column to the benthos and subsequent longer-term recruitment over 15-months. Brief periods of slack currents (<3-hours) retained larvae in unconstrained larval supply treatments, resulting in settlement rates 40-times higher than natural, background rates. Constrained and longer retention of larvae under nets for 2.5- and 24-hours resulted in 4-7-times higher initial settlement than the unconstrained treatment and 305-times higher than background rates. However, after 15-months, similar numbers of surviving recruits were observed across all larval supply treatments, highlighting the effects of density-dependent population regulation. Observations from recruitment tiles show survival rates of coral recruits after 15-months were low (<0.25), even though gregarious settlement behaviour and settlement close to tile edges improved survival. In contrast, observations from the natural substrate show survival rates were 2.5-3.5-times higher than tiles after 15-months, indicating density-independent survival due to optimal niche space and less space limitation. Therefore, when larval supply is high and gregarious behaviour prominent, key vital rates including recruitment and mortality derived from settlement tiles are likely overestimated, as substrate and microhabitat properties between tiles and natural reef environment vary. Overall, our study highlights the prominent role of slack current conditions and local retention of larvae in facilitating the supply-to-settlement transition, and how this interacts with density-dependent processes post-settlement. Our findings underscore the need to investigate how the interaction strengths of pre-and post-settlement processes modulate early coral recovery to best model recovery trajectories for conservation and restoration prioritisation.

ecology↗

bioRxiv2024

Going with the flow: leveraging reef-scale hydrodynamics for upscaling larval-based restoration

Anthropogenic pressures are impacting coastal marine ecosystems, necessitating large-scale interventions to accelerate recovery. Propagule-based restoration holds the potential for restoring shallow coastal systems at hectare scales by harnessing natural dispersal. However, predicting propagule dispersal remains challenging due to the complex hydrodynamic nature of coastal marine ecosystems and the complex behaviours of marine propagules. To improve predictions of fine-scale larval dispersal patterns, we developed a 3D reef-scale ([~]30 m resolution) dispersal model for Lizard Island, Australia, with the aim to predict the effect of island scale hydrodynamics on the distribution of coral spawn slicks and larvae. Using in situ field observations, and dispersal simulations, we assessed the models capability to (1) forecast hydrodynamic conditions, (2) predict coral spawn slick convergence zones for collection efforts, and (3) identify optimal locations and timeframes where high particle residence time may enhance local settlement following larval delivery to damaged reefs. Predictions of convergence zones in the upper water column aligned well with field observations of coral spawn slicks. At the reef benthos, the model captured variability in current speed and direction at [~]58% of studied locations. At other locations, the model did not resolve hydrodynamic conditions due to sheltering effects and associated hydrodynamic processes occurring at a scale below 50 m. At locations where the model performed well, propagules could remain within a one-hectare area around the delivery site for 5 to 15 hours depending on locations and the timing of larval release. These high retention conditions were infrequent but occurred at least once at 15 of the 25 studied sites. Observations of local currents a posteriori confirmed model predictions, showing periods of little water movement lasting from 6.5 to 15 hours. Overall, our study highlights fine-scale dispersal modelling as a key tool for scaling up larval-based reef restoration, while also acknowledging the need for better predictions of local conditions in complex, shallow environments. Applications of fine-scale modelling, coupled with local knowledge of reproductive timing and larval behavioural ecology, assist with the mass collection of propagules upon release and in identifying areas and times of optimal larval deployment to achieve the greatest impact.

ecology↗

bioRxiv2024

Aspergillus-mediated allergic airway inflammation is triggered by dendritic cell recognition of a defined spore morphotype, a process that can be targeted via antifungal therapeutics.

BackgroundExposure to fungi, especially Aspergillus fumigatus (A.f.), can elicit potent allergic inflammation that triggers and worsens asthmatic disease. Dendritic cells (DCs), initiate allergic inflammatory responses to allergic stimuli. However, it is unclear if A.f. spores during isotropic growth (early spore swelling) can activate DCs to initiate allergic responses or if germination is required. This lack of basic understanding of how A.f. causes disease is a barrier to the development of new treatments. ObjectiveTo show that a precise A.f. morphotype stage during spore swelling can trigger DCs to mediate allergic inflammatory responses and ascertain if antifungal therapeutics can be effective at suppressing this process. MethodsWe employed an A.f. strain deficient in pyrimidine biosynthesis ({Delta}pyrG) to generate populations of A.f. spores arrested at different stages of isotropic growth (swelling) via temporal removal of uracil and uridine from growth media. These arrested spore stages were cultured with bone marrow derived DCs (BMDCs), and their activation measured via flow cytometry and ELISA to interrogate which growth stage was able to activate BMDCs. These BMDCs were then adoptively transferred into the airways, to assess if they were able to mediate allergic inflammation in naive recipient mice. Allergic airway inflammation in vivo was determined via flow cytometry, ELISA and qPCR. This system was also used to determine if antifungal drug (itraconazole) treatment could alter early stages of spore swelling and therefore BMDC activation and in vivo allergic inflammation upon adoptive transfer. ResultsWe found that A.f. isotropic growth is essential to trigger BMDC activation and mediate allergic airway inflammation. Furthermore, using time arrested A.f. stages, we found that least 3h in growth media enabled spores to swell sufficiently to activate BMDCs to elicit allergic airway inflammation in vivo. Incubation of germinating A.f. with itraconazole reduced spore swelling and partially reduced their ability to activate BMDCs to elicit in vivo allergic airway inflammation. ConclusionIn summary, our results have pinpointed the precise stage of A.f. development when germinating spores are able to activate DCs to mediate downstream allergic airway inflammation. Furthermore, we have identified that antifungal therapeutics can be effective in reducing the potential of A.f. spores to stimulate allergic responses, highlighting a potential mechanism by which antifungal treatment might help to prevent the development of fungal allergy.

immunology↗

bioRxiv2018

Proteome thermal stability reflects organ physiology and identifies drug-target engagement in vivo

Studying biological processes at a molecular level and monitoring drug-target interactions is established for simple cell systems but challenging in vivo. We introduce and apply a methodology for proteome-wide thermal stability measurements to characterize organ physiology and activity of many fundamental biological processes across tissues, such as energy metabolism and protein homeostasis. This method, termed tissue thermal proteome profiling (tissue-TPP), also enabled target and off-target identification and occupancy measurements in tissues derived from animals dosed with the non-covalent histone deacetylase inhibitor, panobinostat. Finally, we devised blood-CETSA, a thermal stability-based method to monitor target engagement in whole blood. Our study generates the first proteome-wide map of protein thermal stability in tissue and provides tools that will be of great impact for translational research.

cell biology↗

bioRxiv2018

Characterization of novel inhibition of indoleamine 2,3-dioxygenase by targeting its apo form.

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of established and novel IDO1 inhibitors remains of great interest. Comparison of a newly-developed IDO1 inhibitor (GSK5628) to the existing best-in-class compound, epacadostat (Incyte), allows us to report on a unique inhibition mechanism for IDO1. Here, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1) while epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition may help design superior inhibitors or may confer a unique competitive advantage over other IDO1 inhibitors vis-a-vis specificity and pharmacokinetic parameters.

biochemistry↗

bioRxiv2017

Catching up to a fast-moving target: Evaluation of a health system strengthening intervention in rural Rwanda 2005-2010 using data from repeated cross-sectional surveys

IntroductionAlthough Rwandas health system underwent major reforms and improvements after the 1994 Genocide, the health system and population health in the southeast lagged behind other areas. In 2005 Partners In Health and the Rwandan Ministry of Health began a health system strengthening intervention in this region.\n\nMethodsCombining results from the 2005 and 2010 Demographic and Health Surveys with those from a supplemental 2010 survey, we compared changes in health system output indicators and population health outcomes between 2005 and 2010 as reported by 21,338 women living in the intervention area and similar rural areas, controlling for potential confounding by economic and demographic variables.\n\nResultsOverall health system coverage improved similarly in both regions between 2005 and 2010, with an indicator of composite coverage of child health interventions increasing from 57.9% to 75.0% in the intervention area and from 58.7% to 73.8% in other rural areas. Despite experiencing poorer health outcomes in 2005, the intervention area caught up to or exceeded other rural areas on 23 of 25 indicators. Most notably, under-five mortality declined by an annual rate of 12.8% in the intervention area, from 229.8 to 83.2 deaths per 1000 live births, and by 8.9% in other rural areas, from 157.7 to 75.8 deaths per 1000 live births. Improvements were most dramatic among the poorest households.\n\nConclusionWe observed dramatic improvements in population health outcomes including under-five mortality between 2005 and 2010 in rural Rwanda generally, and in the intervention area specifically.\n\nSUMMARY BOXO_ST_ABSWhat is already known about this topic?C_ST_ABSO_LIMuch of the evidence that health system strengthening in rural Africa has improved health outcomes comes from studies of targeted regional interventions such as performance based financing or community health worker programs, rather than integrated interventions that encompass multiple components including infrastructure and supply chain investments, health management information system, workforce training and incentives at all levels, community health workers, and free services for poor patients.\nC_LIO_LIIn addition to these experimental or quasi-experimental studies, a series of case studies have documented individual nations, pathways to achieving millennium development goal 4 target, the reduction of under-five mortality by two thirds between 1990 and 2015.\nC_LIO_LIThese reports suggest that improvements in coverage of reproductive, maternal and child health indicators explain some, but not all, of the decline in child mortality and that these successes occurred in the context of national gains in health, nutrition and food security, sanitation, poverty reduction, and access to clean water.\nC_LI\n\nWhat are the new findings?O_LICoverage of most maternal and child health care interventions improved at a similar pace in our rural intervention area and other rural areas.\nC_LIO_LIDespite experiencing poorer health outcomes in 2005, our rural intervention area caught up to or exceeded other rural areas on 23 of 25 population health indicators by 2010.\nC_LIO_LIInfant and under-5 mortality declined in our rural intervention area even more precipitously than in other rural areas of Rwanda between 2005 and 2010.\nC_LI\n\nHow might this influence practice?O_LIThe process of strengthening national health systems often involves trade-offs between a focus on first testing individual programs that distributed widely, as is often practiced by pilot programs with multilateral institutions, or implementing multiple simultaneous programs locally. Our results show that integrated health system strengthening interventions can be locally adapted to enable the rapid expansion of health care coverage as well as dramatic improvements in population health outcomes.\nC_LIO_LIIntegrated multi-level interventions can also help narrow the health care coverage and outcome gap between richer and poorer members of a society.\nC_LIO_LINational governments can leverage nongovernmental partners to achieve the health related sustainable development goals through joint implementation of national health policy.\nC_LI

epidemiology↗